Fight Aging!

In mammals, reduced levels of myostatin or increased levels of follistatin, which acts to inhibit myostatin production, can be achieved by a variety of methods ranging from gene therapy to RNA interference, the standard panoply of technologies used to adjust the amounts of a particular protein in animal studies. Suitably altered levels of myostatin or follistatin result in greatly increased muscle growth, lower amounts of body fat, and in mice at least a possible but disputed modest life extension to go along with it. The most direct methodology is knockout of the myostatin gene, and this is the path chosen of late by Chinese researchers in their work on dogs, using CRISPR, one of the latest advances in genetic editing technology.

The creation of genetically altered, heavily muscled dogs is not an isolated line of research. There is at least one dog breed in which a myostatin mutation has occurred naturally, and the same goes for cows, another species heavily influenced by centuries of quite sophisticated human breeding strategies. There are even a few human natural myostatin mutants presently alive, as well-muscled as their animal peers. Gene therapies have been used for nearly a decade to create "mighty mouse" myostatin and follistatin mutants. Early this year scientists demonstrated myostatin knockout pigs using TALENs, another modern improvement on older methods of gene therapy.

Obviously this is a road that at some point branches away from the production of improved animal lineages towards the production of enhancements and therapies for humans. The conventional view is that enhanced muscle production is a viable therapy for the collection of wasting diseases known as myopathies and sarcopenia, the characteristic progressive loss of muscle mass and strength that occurs with aging. This would be a compensatory approach, a way to improve quality of life by overriding some of the results of damage or disease on the natural balance of muscle tissue repair and regeneration, but without actually fixing the damage itself.

I have in the past argued that myostatin or follistatin gene therapies look very much like an all upside treatment, something that everyone should undergo in an ideal world, not just older or sicker people, after it has been developed for use in humans. On the other hand SENS Research Foundation staffer Michael Rae has suggested more caution; if you look back at some of the archived posts on animal studies of myostatin knockout you'll see some of the data to back up that point of view. A decade of animal studies, naturally occurring mutant lineages, numerous mammalian examples of successful gene therapy, and early human trials of the same for myopathies is enough for some people, however. It is interesting to note that BioViva CEO Liz Parrish recently became the first publicly acknowledged healthy recipient of follistatin gene therapy, carried out as a first step towards spurring greater progress towards human clinical trials and treatments aimed at slowing or reversing the effects of aging.

All in all, if you were going to pick one gene therapy to move on with today, myostatin or follistatin would be near the top of the list given the present state of the art and the level of experience present in the scientific community. This is no doubt why the researchers here chose it as a first step in their program of producing genetically altered dog lineages. Their ultimate goal is the production of new models for disease research, not enhancement or treatments per se, but work on myostatin is sufficiently well advanced that it makes a good test case for the newer technologies and methodologies used along the way.

First Gene-Edited Dogs Reported in China

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin. The dogs have "more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications. The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research. Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics."

Genome editing refers to newly developed techniques that let scientists easily disable genes or rearrange their DNA letters. The method used to change the beagles, known as CRISPR-Cas9, is particularly inexpensive and precise. Last month, the work was highlighted as part of a large Chinese effort to modify animals using CRISPR. The list of animals already engineered using gene editing in China includes goats, rabbits, rats, and monkeys. The efforts were described as a national scientific priority and part of China's effort to establish world-class research.

The dog researchers took much the same approach, directly introducing the gene-editing chemicals - a DNA snipping enzyme, Cas9, and a guide molecule that zeroes in to a particular stretch of DNA - into more than 60 dog embryos. Their objective was to damage, or knock out, both copies of the myostatin gene so that the beagles' bodies would not produce any of the muscle-inhibiting protein that the gene manufactures. In the end, of 65 embryos they edited, 27 puppies were born, but only two, a female and a male, had disruptions in both copies of the myostatin gene. They named the female Tiangou, after the "heaven dog" in Chinese myth. They named the male Hercules. In Hercules the gene editing was incomplete, and that a percentage of the dog's muscle cells were still producing myostatin. But in Tiangou, the disruption of myostatin was complete and the beagle "displayed obvious muscular phenotype," or characteristics.